SPC365

Alpha-tropomyosin gene variants in Hypertrophic Cardiomyopathy: clinical features and disease progression

Session: SESSÃO DE POSTERS 57 - MIOCARDIOPATIA HIPERTRÓFICA
Speaker: Marta Vilela

Congress: CPC 2025
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.2 Myocardial Disease – Epidemiology, Prognosis, Outcome
Session Type: Cartazes
FP Number: ---
Authors: Marta Miguez Vilela; Catarina Gregório; Beatriz Garcia; Ana Abrantes; João Cravo; Diogo Ferreira; Daniel Cazeiro; Oana Moldovan; Hugo Madeira; Fausto Pinto; Dulce Brito

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Introduction:</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif">Sarcomere Hypertrophic Cardiomyopathy (HCM) is an autosomal-dominant disease with variable genotypic and phenotypic expressions. Alpha-tropomyosin (TPM1) variants account for 1&ndash;5% of cases, but their clinical significance and role in disease progression remain poorly understood. </span></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Purpose:</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif">To analyse the HCM phenotype and the evolutive profile in TPM1-HCM families.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Methods</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif">A retrospective analysis of HCM patients (probands and affected relatives) followed in a tertiary center was performed, considering only those with TPM1 pathogenic/likely pathogenic variant. To assess clinical outcomes, a composite outcome of all-cause mortality and cardiovascular (CV) hospitalizations was defined.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Results:</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif">This study included 15 probands with HCM from unrelated families, totalling 48 individuals. Among them, 24 were mutation carriers without phenotypic (Ph-) expression, while 24 exhibited Ph expression. At diagnosis the mean age was 48&plusmn;3.9 years in the HCM group and 35&plusmn; 3.2years in carriers Ph-, with a similar proportion of females in both groups. Most individuals carry the p.Arg21Leu variant&nbsp; (n=38; 79%), while the remainder have the p.Met281Val variant (n=10; 21%). </span></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif">In the HCM group, 54% were diagnosed due to symptoms (mainly chest pain), 38% through family screening and 8% by incidental findings. At baseline, 4 patients had LVOT obstruction, the mean left atrial size was 45 &plusmn; 1.9 mm and the maximum wall thickness was 17.7 (&plusmn; 1.1) mm. The proportion of patients considered at intermediate or high risk for sudden death (ESC score) increased from 4% to 29% at follow-up (FUP). Two patients underwent septal reduction therapy, and 2 patients implanted cardioverter defibrillator in primary prevention. The <span style="background-color:white">median FUP time was 11.8 years (IQR 7.22&ndash;16.36</span>). Only 1 mutation carrier Ph- at baseline progressed to HCM. Among HCM patients, 6 (25%) developed non-sustained ventricular tachycardia, 1 (5%) had atrial fibrillation and 1 (4%) developed a ventricular aneurysm. The composite event occurred in 5 HCM patients (21%). Significant associations were found between the composite outcome and NT-proBNP levels at diagnosis [377 pg/mL (IQR 196-558) vs. 3200 pg/mL (IQR 2950-3450); p=0.019], left atrial size (43.3 &plusmn; 2 mm vs. 51.4 &plusmn; 4.3 mm; p=0.05) and age at diagnosis (p=0.023). HCM patients had a 6-fold increased risk of death or hospitalization compared to carriers Ph- (p=0.012, OR 6.2).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Conclusion:</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:18px"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif">In this cohort of HCM patients, TPM1 mutations were associated with clinical variability in disease expression, with some key predictors of a worse prognosis: increased NT-proBNP levels, enlarged left atrial size and older age at diagnosis. </span></span></span></p>